Study of XL281 in Adults With Solid Tumors

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To assess the pharmacokinetic/pharmacodynamic/preliminary clinical activity relationship following XL281 administration in different tumor types from subjects treated at the MTD [ Time Frame: Assessed at periodic visits ]

To determine the bioavailability of XL281 under fed and fasted conditions, and with or without the concomitant use of a single dose of famotidine in subjects with solid tumors [ Time Frame: Assessed during the second, third, and fourth week of the first cycle of dosing ]

Plasma pharmacokinetics of once daily or twice daily oral administration of XL281 [ Time Frame: Assessed at periodic visits ]

Original Secondary Outcome Measures ICMJE (submitted: March 23, 2007)

Plasma pharmacokinetics of daily oral administration of XL281

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Study of XL281 in Adults With Solid Tumors

Official Title ICMJE

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL281 Administered Orally to Subjects With Solid Tumors

Brief Summary

The purpose of this study is to determine the safest dose of the multiple Raf kinase inhibitor (including c-Raf, B-Raf, and the activated mutant B-RafV600E) XL281, how often it should be taken, and how well subjects with cancer tolerate XL281. This study will also determine how the body reacts to XL281 when it is taken with and without food, and with and without Pepcid (famotidine), a drug that inhibits stomach acid production.

XL281 administered once a day. Subjects in this arm will be dosed under fed conditions, fasted conditions, and with a concomitant single dose of 40 mg famotidine, during the second, third, and fourth week of the first cycle.

Interventions:

Drug: XL281

Drug: famotidine

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Estimated Enrollment ICMJE

180

Completion Date

October 2011

Primary Completion Date

October 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Key Inclusion Criteria:

The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no therapies known to prolong survival. Subjects treated at the MTD (once- or twice- daily) must have a diagnosis of colorectal cancer, non-small-cell lung cancer (no longer recruiting), melanoma, or papillary thyroid cancer. Certain other eligibility requirements must also be met.

The subject is ≥18 years old.

The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

The subject has adequate organ and marrow function.

The subject is capable of understanding the protocol and has signed the informed consent document.

Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months after study drug discontinuation.

Female subjects of childbearing potential must have a negative pregnancy test at screening.

The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed ≥5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

The subject must meet certain other eligibility requirements.

Key Exclusion Criteria:

The subject has received anticancer treatment (eg, chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C) before the first dose of study drug.

The subject has received treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within a certain amount of time before the first dose of study drug.

The subject has received any other investigational agent within 28 days of first dose of XL281.

The subject has not recovered to Grade ≤1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 30 days prior to study enrollment. Some irreversible toxicities from previous treatment may be allowed.